Hypophosphatemia

Definition, Etiology, PathogenesisTop

Hypophosphatemia is defined as a serum inorganic phosphate [Pi] <0.9 mmol/L (<2.8 mg/dL).

Causes:

1) Insufficient dietary Pi intake due to chronic protein malnutrition.

2) Impaired gastrointestinal (GI) absorption of Pi due to ingestion of substances that bind Pi (most frequently antacids), vitamin D deficiency, or malabsorption syndromes.

3) Excessive renal Pi loss due to hyperparathyroidism, excess of phosphatonins (secreted by certain cancers), vitamin D deficiency, glucocorticoids, or congenital or acquired renal tubulopathies.

4) A shift of Pi from the extracellular to the intracellular compartment caused by respiratory alkalosis, refeeding syndrome, the blood glucose normalization phase during treatment of diabetic ketoacidosis, so-called hungry bone syndrome after parathyroidectomy, or the anabolic phase after severe trauma.

The most common clinical situations in which hypophosphatemia should be expected include respiratory alkalosis, intensive treatment of diabetic ketoacidosis, long-term use of antacids, and nutritional treatment of malnourished patients. Phosphate deficiency leads to decreased synthesis of adenosine triphosphate (ATP) and other high-energy phosphate compounds, which considerably impairs functioning of all cells in the body and leads to osteomalacia.

Clinical FeaturesTop

Clinical manifestations of hypophosphatemia depend on the severity of phosphate depletion and on the rate at which it developed. Chronic mild and moderate hypophosphatemia may be asymptomatic for a long time or manifest as bone pain and muscle weakness. Severe acute hypophosphatemia may manifest as muscle weakness including respiratory compromise paralysis or even rhabdomyolysis, intention tremor, seizures or even coma, hemolysis, bleeding due to platelet disorders, features of liver injury, and severe infections.

DiagnosisTop

The diagnosis of hypophosphatemia is based on measurement of serum [Pi] (<0.9 mmol/L [<2.8 mg/dL]).

History may suggest the pathogenesis of hypophosphatemia. Studies useful in establishing the cause of hypophosphatemia include serum levels of calcium, potassium, magnesium, parathyroid hormone (PTH), and vitamin D; blood gas analysis; urinalysis; and measurement of urinary Pi excretion.

TreatmentTop

1. Treatment of the underlying condition is the mainstay of the management of hypophosphatemia.

2. Correct body phosphate deficiency:

1) Recommend a high-phosphate diet (see Phosphate Disturbances).

2) Administer oral repletion: 30 to 80 mmol of phosphate per day in divided doses over a 24-hour period. Commonly used oral supplements include sodium phosphate or potassium phosphate (a 250 mg tablet contains 8 mmol Pi). Serum [Pi] should be rechecked 2 to 6 hours after the last dose to determine if additional doses are required.

3) In patients with hypophosphatemia and serious symptoms and in those unable to take oral medication, administer an IV sodium or potassium phosphate solution at a dose of 15 to 30 mmol over 2 to 6 hours. Remeasure serum [Pi] and calcium levels.